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5vsm

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Revision as of 16:56, 20 November 2019

Crystal structure of viperin with bound [4Fe-4S] cluster, 5'-deoxyadenosine, and L-methionine

Structural highlights

5vsm is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5vsl
Gene:	Rsad2, Vig1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RSAD2_MOUSE] Interferon-inducible iron-sulfur (4FE-4S) cluster-binding antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Can inhibit a wide range of viruses, including west Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, sendai virus and vesicular stomatitis virus (VSV). Displays antiviral activity against influenza A virus by inhibiting the budding of the virus from the plasma membrane by disturbing the lipid rafts. This is accomplished, at least in part, through binding and inhibition of the enzyme farnesyl diphosphate synthase (FPPS), which is essential for the biosynthesis of isoprenoid-derived lipids. Promotes TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating Lys-63'-linked ubiquitination of IRAK1. Plays a role in CD4+ T-cells activation and differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble proteins.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Viperin is an IFN-inducible radical S-adenosylmethionine (SAM) enzyme that inhibits viral replication. We determined crystal structures of an anaerobically prepared fragment of mouse viperin (residues 45-362) complexed with S-adenosylhomocysteine (SAH) or 5'-deoxyadenosine (5'-dAdo) and l-methionine (l-Met). Viperin contains a partial (betaalpha)6-barrel fold with a disordered N-terminal extension (residues 45-74) and a partially ordered C-terminal extension (residues 285-362) that bridges the partial barrel to form an overall closed barrel structure. Cys84, Cys88, and Cys91 located after the first beta-strand bind a [4Fe-4S] cluster. The active site architecture of viperin with bound SAH (a SAM analog) or 5'-dAdo and l-Met (SAM cleavage products) is consistent with the canonical mechanism of 5'-deoxyadenosyl radical generation. The viperin structure, together with sequence alignments, suggests that vertebrate viperins are highly conserved and that fungi contain a viperin-like ortholog. Many bacteria and archaebacteria also express viperin-like enzymes with conserved active site residues. Structural alignments show that viperin is similar to several other radical SAM enzymes, including the molybdenum cofactor biosynthetic enzyme MoaA and the RNA methyltransferase RlmN, which methylates specific nucleotides in rRNA and tRNA. The viperin putative active site contains several conserved positively charged residues, and a portion of the active site shows structural similarity to the GTP-binding site of MoaA, suggesting that the viperin substrate may be a nucleoside triphosphate of some type.

Structural studies of viperin, an antiviral radical SAM enzyme.,Fenwick MK, Li Y, Cresswell P, Modis Y, Ealick SE Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):6806-6811. doi:, 10.1073/pnas.1705402114. Epub 2017 Jun 12. PMID:28607080^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang Y, Burke CW, Ryman KD, Klimstra WB. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication. J Virol. 2007 Oct;81(20):11246-55. Epub 2007 Aug 8. PMID:17686841 doi:http://dx.doi.org/JVI.01282-07
↑ Qiu LQ, Cresswell P, Chin KC. Viperin is required for optimal Th2 responses and T-cell receptor-mediated activation of NF-kappaB and AP-1. Blood. 2009 Apr 9;113(15):3520-9. doi: 10.1182/blood-2008-07-171942. Epub 2008, Dec 1. PMID:19047684 doi:http://dx.doi.org/10.1182/blood-2008-07-171942
↑ Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity. 2011 Mar 25;34(3):352-63. doi: 10.1016/j.immuni.2011.03.010. PMID:21435586 doi:http://dx.doi.org/10.1016/j.immuni.2011.03.010
↑ Szretter KJ, Brien JD, Thackray LB, Virgin HW, Cresswell P, Diamond MS. The interferon-inducible gene viperin restricts West Nile virus pathogenesis. J Virol. 2011 Nov;85(22):11557-66. doi: 10.1128/JVI.05519-11. Epub 2011 Aug 31. PMID:21880757 doi:http://dx.doi.org/10.1128/JVI.05519-11
↑ Fenwick MK, Li Y, Cresswell P, Modis Y, Ealick SE. Structural studies of viperin, an antiviral radical SAM enzyme. Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):6806-6811. doi:, 10.1073/pnas.1705402114. Epub 2017 Jun 12. PMID:28607080 doi:http://dx.doi.org/10.1073/pnas.1705402114

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5vsm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of viperin with bound [4Fe-4S] cluster, 5'-deoxyadenosine, and L-methionine==
-<StructureSection load='5vsm' size='340' side='right' caption='[[5vsm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='5vsm' size='340' side='right'caption='[[5vsm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vsm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vsm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSM FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vsl|5vsl]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rsad2, Vig1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vsm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsm OCA], [http://pdbe.org/5vsm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vsm RCSB], [http://www.ebi.ac.uk/pdbsum/5vsm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsm ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Cresswell, P]]
 [[Category: Ealick, S E]]

5vsm

From Proteopedia

Revision as of 16:56, 20 November 2019

Crystal structure of viperin with bound [4Fe-4S] cluster, 5'-deoxyadenosine, and L-methionine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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